Journal article
Calmodulin Regulation of Excitation-Contraction Coupling in Cardiac Myocytes
Circulation research, Vol.92(6), pp.659-667
04/04/2003
DOI: 10.1161/01.RES.0000064566.91495.0C
PMID: 12609973
Abstract
Calmodulin (CaM) as a ubiquitous Ca2+ sensor interacts with multiple key molecules involved in excitation-contraction (EC) coupling. In the present study, we report that adenoviral expression of a mutant CaM lacking all of its four Ca2+-binding sites, CaM(1-4), at a level 6.5-fold over endogenous CaM markedly increases the amplitude and abbreviates the decay time of Ca2+ transients and contraction in cultured rat ventricular myocytes. To determine the underlying mechanisms, we examined the properties of L-type Ca2+ channels, Ca2+/CaM-dependent protein kinase II (CaMKII), and phospholamban (PLB) in the sarcoplasmic reticulum (SR). We found that CaM(1-4) expression markedly augmented L-type Ca2+ current amplitude and slowed its inactivation. Surprisingly, overexpression of CaM(1-4) increased CaMKII activity and phosphorylation of PLB-Thr-17. Moreover, CAM(1-4) elevated diastolic Ca2+ and caffeine-labile Ca2+ content of the SR. Inhibition of CaMKII by KN-93 or a myristoylated autocamtide-2 related inhibitory peptide prevented the aforementioned PLB phosphorylation and reversed the positive inotropic and relaxant effects, indicating that CaMKII is essential to CaM(1-4) actions. These results demonstrate that CaM modulates Ca2+ influx, SR Ca2+ release, and Ca2+ recycling during cardiac EC coupling. A novel finding of this study is that expression of a Ca2+-insensitive CaM mutant can lead to activation of CaMKII in cardiac myocytes.
Details
- Title: Subtitle
- Calmodulin Regulation of Excitation-Contraction Coupling in Cardiac Myocytes
- Creators
- Dongmei Yang - From the National Laboratory of Biomembrane and Membrane Biotechnology (D.Y., C.W., H.C.), College of Life Sciences, Peking University, Beijing, China; Laboratory of Cardiovascular Sciences (D.Y., L.-S.S., W.-Z.Z., K.C., W.W., R.-P.X., H.C.), National Institute on Aging, National Institutes of Health, Baltimore, Md; the Department of Physiology (Y.W.), School of Medicine, University of Maryland, Baltimore, Md; Cardiovascular Research Group (S.R.W.C.), Departments of Physiology & Biophysics andLong-Sheng Song - From the National Laboratory of Biomembrane and Membrane Biotechnology (D.Y., C.W., H.C.), College of Life Sciences, Peking University, Beijing, China; Laboratory of Cardiovascular Sciences (D.Y., L.-S.S., W.-Z.Z., K.C., W.W., R.-P.X., H.C.), National Institute on Aging, National Institutes of Health, Baltimore, Md; the Department of Physiology (Y.W.), School of Medicine, University of Maryland, Baltimore, Md; Cardiovascular Research Group (S.R.W.C.), Departments of Physiology & Biophysics andWei-Zhong Zhu - From the National Laboratory of Biomembrane and Membrane Biotechnology (D.Y., C.W., H.C.), College of Life Sciences, Peking University, Beijing, China; Laboratory of Cardiovascular Sciences (D.Y., L.-S.S., W.-Z.Z., K.C., W.W., R.-P.X., H.C.), National Institute on Aging, National Institutes of Health, Baltimore, Md; the Department of Physiology (Y.W.), School of Medicine, University of Maryland, Baltimore, Md; Cardiovascular Research Group (S.R.W.C.), Departments of Physiology & Biophysics andKhalid Chakir - From the National Laboratory of Biomembrane and Membrane Biotechnology (D.Y., C.W., H.C.), College of Life Sciences, Peking University, Beijing, China; Laboratory of Cardiovascular Sciences (D.Y., L.-S.S., W.-Z.Z., K.C., W.W., R.-P.X., H.C.), National Institute on Aging, National Institutes of Health, Baltimore, Md; the Department of Physiology (Y.W.), School of Medicine, University of Maryland, Baltimore, Md; Cardiovascular Research Group (S.R.W.C.), Departments of Physiology & Biophysics andWei Wang - From the National Laboratory of Biomembrane and Membrane Biotechnology (D.Y., C.W., H.C.), College of Life Sciences, Peking University, Beijing, China; Laboratory of Cardiovascular Sciences (D.Y., L.-S.S., W.-Z.Z., K.C., W.W., R.-P.X., H.C.), National Institute on Aging, National Institutes of Health, Baltimore, Md; the Department of Physiology (Y.W.), School of Medicine, University of Maryland, Baltimore, Md; Cardiovascular Research Group (S.R.W.C.), Departments of Physiology & Biophysics andCaihong Wu - From the National Laboratory of Biomembrane and Membrane Biotechnology (D.Y., C.W., H.C.), College of Life Sciences, Peking University, Beijing, China; Laboratory of Cardiovascular Sciences (D.Y., L.-S.S., W.-Z.Z., K.C., W.W., R.-P.X., H.C.), National Institute on Aging, National Institutes of Health, Baltimore, Md; the Department of Physiology (Y.W.), School of Medicine, University of Maryland, Baltimore, Md; Cardiovascular Research Group (S.R.W.C.), Departments of Physiology & Biophysics andYibin Wang - From the National Laboratory of Biomembrane and Membrane Biotechnology (D.Y., C.W., H.C.), College of Life Sciences, Peking University, Beijing, China; Laboratory of Cardiovascular Sciences (D.Y., L.-S.S., W.-Z.Z., K.C., W.W., R.-P.X., H.C.), National Institute on Aging, National Institutes of Health, Baltimore, Md; the Department of Physiology (Y.W.), School of Medicine, University of Maryland, Baltimore, Md; Cardiovascular Research Group (S.R.W.C.), Departments of Physiology & Biophysics andRui-Ping Xiao - From the National Laboratory of Biomembrane and Membrane Biotechnology (D.Y., C.W., H.C.), College of Life Sciences, Peking University, Beijing, China; Laboratory of Cardiovascular Sciences (D.Y., L.-S.S., W.-Z.Z., K.C., W.W., R.-P.X., H.C.), National Institute on Aging, National Institutes of Health, Baltimore, Md; the Department of Physiology (Y.W.), School of Medicine, University of Maryland, Baltimore, Md; Cardiovascular Research Group (S.R.W.C.), Departments of Physiology & Biophysics andS.R. Wayne Chen - From the National Laboratory of Biomembrane and Membrane Biotechnology (D.Y., C.W., H.C.), College of Life Sciences, Peking University, Beijing, China; Laboratory of Cardiovascular Sciences (D.Y., L.-S.S., W.-Z.Z., K.C., W.W., R.-P.X., H.C.), National Institute on Aging, National Institutes of Health, Baltimore, Md; the Department of Physiology (Y.W.), School of Medicine, University of Maryland, Baltimore, Md; Cardiovascular Research Group (S.R.W.C.), Departments of Physiology & Biophysics andHeping Cheng - From the National Laboratory of Biomembrane and Membrane Biotechnology (D.Y., C.W., H.C.), College of Life Sciences, Peking University, Beijing, China; Laboratory of Cardiovascular Sciences (D.Y., L.-S.S., W.-Z.Z., K.C., W.W., R.-P.X., H.C.), National Institute on Aging, National Institutes of Health, Baltimore, Md; the Department of Physiology (Y.W.), School of Medicine, University of Maryland, Baltimore, Md; Cardiovascular Research Group (S.R.W.C.), Departments of Physiology & Biophysics and
- Resource Type
- Journal article
- Publication Details
- Circulation research, Vol.92(6), pp.659-667
- DOI
- 10.1161/01.RES.0000064566.91495.0C
- PMID
- 12609973
- ISSN
- 0009-7330
- eISSN
- 1524-4571
- Language
- English
- Date published
- 04/04/2003
- Academic Unit
- Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Internal Medicine
- Record Identifier
- 9984094585402771
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